Genomic Landscape and Immunological Profile of Glioblastoma in East Asian Patients

Abstract While it is well known that Glioblastoma (GBM) shows profound inter- and intra-tumoral heterogeneity, disparities in molecular features across ancestry groups have been largely overlooked. We collected a large cohort of GBM samples from East Asian patients (EAS-GBM) and performed genomic and transcriptomic analyses of these samples (EAS-GBM, n=443). Further characterization and comparative analysis of the EAS-GBM with the predominantly European-ancestry TCGA GBM dataset (EUR-GBM, n=383) revealed differential genomic and genetic landscape and immunological profile of EAS-GBM from EUR-GBM. EAS-GBM showed an enrichment for NF1, H3F3A, TP53 and ATRX mutations compared to EUR-GBM. Transcriptomic clustering revealed distinct EAS-GBM specific subtypes, namely Proliferative (PL), Neuron-Synaptic (NS), Metabolic (MB) and Immunomodulatory (IM). Notably, the classic subtype of EUR-GBMs with EGFR as its main marker gene was absent in EAS-GBMs, Moreover, the IM subgroup in EAS-GBM with an expression profile that has been previously associated with response to immunotherapy in cancers. Together, our comprehensive characterization revealed the unique genomic and genetic features of EAS-GBMs, providing mechanistic rationale in patient stratification for molecular targeted therapy and drug development in the era of personalized medicine.